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1 Electronic Supplementary Material (ESI) for Dalton Transactions. This journal is The Royal Society of Chemistry 2018 Electronic Supplementary Information (ESI) Palladium(II) and platinum(ii) saccharinate complexes with bis(diphenylphosphino)methane/ethane: synthesis, S-phase arrest and ROS-mediated apoptosis in human colon cancer cells Ceyda Icsel, a Veysel T. Yilmaz,* a Muhittin Aygun, b Buse Cevatemre, c Pinar Alper d and Engin Ulukaya d a Department of Chemistry, Faculty of Arts and Sciences, Uludag University, Bursa, Turkey. b Department of Physics, Faculty of Sciences, Dokuz Eylul University, Izmir, Turkey c Department of Biology, Faculty of Arts and Sciences, Uludag University, Bursa, Turkey. d Department of Medical Biochemistry, Faculty of Medicine, University of Istinye, Istanbul, Turkey Corresponding Author: Prof. Dr. Veysel T. Yilmaz Department of Chemistry Faculty of Arts and Sciences Uludag University Bursa, Turkey vtyilmaz@uludag.edu.tr 1

2 Table S1 Crystallographic data and structure refinement for complexes empirical formula C 39H 32N 2O 7P 2PdS 2 C 41H 36N 2O 7P 2PtS 3 C 64H 52N 2O 6P 4PdS 2 C 64H 52N 2O 6P 4PtS 2 C 40H 32N 2O 6P 2PdS 2 C 40H 32N 2O 6P 2PtS 2 C 66H 56N 2O 6P 4PdS 2 C 72H 70N 4O 8P 4PtS 2 formula weight crystal system monoclinic tetragonal triclinic triclinic tetragonal tetragonal monoclinic monoclinic space group P2 1/n I4 1/a P1 P1 P4 2 1c P4 2 1c P2 1/c P2 1/c a, Å (5) (17) (4) (4) (5) (8) (2) (6) b, Å (2) (17) (8) (4) (5) (8) (2) (7) c, Å (4) (9) (6) (5) (8) (9) (2) (9) α, deg (5) (3) β, deg (2) (4) (4)) (13) (5) γ, deg (4) (3) V, Å (3) 17477(2) (14) (10) (4) (5) (8) (3) T, K 293(2) 293(2) 293(2) 293(2) 293(3) 293(2) 293(2) 293(2) Z ρ calc (g cm 3 ) μ (mm 1 ) F(000) ( o ) collected refls data/ parameters / / / / / / / /413 goodness-of-fit R 1 [I>2 ] wr

3 Table S2 Temperature-dependent fluorescence emission titration data for the interaction of the complexes with FS-DNA. Complexes T(K) KSV(M -1 ) x KF(M -1 ) x ΔG (kj/mol) ΔH (kj/mol) ΔS (J/Kmol) Table S3 Temperature-dependent fluorescence emission titration data for the interaction of the complexes with HSA. Complexes T(K) KSV(M -1 ) x KF(M -1 ) x ΔG (kj/mol) ΔH (kj/mol) ΔS (J/Kmol)

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11 Fig. S1 1 H- (a) 13 C- (b) and 31 P-NMR spectra (c) of

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15 Fig. S2 ESI-MS spectra of

16 Fig. S3 The dose-response graphics for 1 8 obtained from SRB assay, showing the effect of the complexes (20 µm) on the growth of the cell lines after 48 h of treatment. 16

17 Fig. S4 UV spectra of the potent complexes, showing their stability in MeOH, DMSO and saline at 0, 24 and 48 h. 17

18 Fig. S5 The dose-response graphics for the potent complexes and cisplatin obtained from ATP assay, showing the effect of the complexes on the growth of the cell lines after 48 h of treatment. 18

19 Fig. S6 Cell cycle progression of HCT116 cells treated with IC90 doses of 1 (50 µm), 3 (30 µm), 4 (20 µm) and cisplatin (44 µm) for 24 h. Fig. S7 ROS generation in HCT116 cells treated with IC90 doses of 1 (50 µm), 3 (30 µm), 4 (20 µm) and cisplatin (44 µm) for 24 and 48 h. 19

20 Fig. S8 (a) Annexin-V positivity and (b) Caspase 3/7 activity in HCT116 cells treated with IC90 doses of 1 (50 µm), 3 (30 µm), 4 (20 µm) and cisplatin (44 µm) for 24 and 48 h. Fig S9 Mitochondrial membrane depolarization in HCT116 cells treated with the IC90 doses of 1 (50 µm), 3 (30 µm), 4 (20 µm) and cisplatin (44 µm) for 24 and 48 h. 20

21 Fig S10 Formation of DNA double-strand breaks in HCT116 cells treated with the IC90 doses of 1 (50 µm), 3 (30 µm), 4 (20 µm) and cisplatin (44 µm) for 6, 12, 24 and 48 h. 21

22 Fig. S11 Time-dependent morphological changes in the nuclei of HCT116 cells induced by the IC90 doses of 1 (50 µm), 3 (30 µm), 4 (20 µm) and cisplatin (44 µm). Cells were stained with Hoechst followed by detection using fluorescence microscope. Magnification:

23 Fig. S12 Absorption titration spectra of FS-DNA solutions (50 μm) with increasing amounts of the potent complexes (0 15 μm) of in Tris-HCl buffer. Inset: plot of 1/[complex] vs. 1/(A A0). 23

24 Fig. S13 Emission titration spectra of EB-bound DNA solutions in the absence and presence of increasing concentrations of the potent complexes (0 50 μm) in Tris-HCl. [EB] = 5 μm, [DNA] = 50 μm. The Inset shows the Stern-Volmer plot of the fluorescence data. Fig. S14 The relative viscosity of FS-DNA (0.8 mm bp) upon addition of increasing amounts of the potent complexes, EB and Hoechst in Tris-HCl buffer. η is the viscosity of DNA in the presence of complex, and η0 is the viscosity of DNA alone. r = [Complex]/[DNA(bp)]. Fig. S15 Thermal denaturation profiles of FS-DNA (100 μm) in the absence and in the presence of the potent complexes (10 μm) in Tris-HCl. 24

25 Fig. S16 UV absorption spectra of HSA (10 μm) upon addition of increasing amounts of the potent complexes (0 10 μm) in Tris-HCl buffer. The arrow shows the increases in absorbance. Inset: plot of 1/[complex] vs. 1/(A A0). 25

26 Fig. S17 Emission spectra of HSA (5 μm; λex = 280 nm) in presence of the potent complexes (0-10 μm). The arrow shows the emission intensity changes upon increasing complex concentration. Insets: Stern-Volmer plot of the fluorescence data. 26

27 (a) (b) Fig. S18 Synchronous spectra of HSA (5 μm) in presence of the potent complexes (0-10 μm) at λ = 15 nm (a) and λ = 60 nm (b). Arrows show the emission intensity changes upon increasing concentration of the complexes. 27

28 Fig. S19 3D fluorescence spectra of HSA (5 μm), and HSA (5 μm) + the potent complexes (5μM) in Tris-HCl buffer. 28